Articular Chondromatosis and Chrondroid Metaplasia in Transgenic TAg Mice

Abstract

The C3(1)/SV40 T antigen transgenic mouse model for which rapid mammary and prostate tumor development has been documented uses the FVB/N mouse as a background strain. In this study, where the background strain used was the C57BL/6J mouse, neither mammary nor prostate tumors developed over periods of up to 40 weeks. However, a disturbance of hyaline cartilage in joints was observed similar to that found in synovial chondromatosis in humans. In addition, cartilage thickening in the external ears and cartilaginous metaplasia of the ascending aorta also occurred. This suggests that rearrangement of the transgene occurred in breeding on the C57BL background, thus modifying its expression. It raises the possibility that the genetic changes induced by the SV40 T antigen transforming sequence are important in cartilage homeostasis.

Keywords

Transgenic TAg mouse hyaline cartilage metaplasia chondromatosis joints artery.

References

Buddingh, E.P. , P. Krallman , J.R. Neff , M. Nelson , J. Liu , and J.A. Bridge (2003). “Chromosome 6 Abnormalities are Recurrent in Synovial Chrondromatosis.” Cancer Genet Cytogenet 143: 1—31.

Edinger, D.T. and P.A. Manley (1998). “Arthrodesis of the Shoulder for Synovial Osteochondromatosis.” J Small Anim Pract 39: 397— 400.

Maroulakou, I.G. , M. Anver , L. Garrett , and J.E. Green (1994). “Prostate and Mammary Adenocarcinoma in Transgenic Mice Carrying a Rat C3(1) Simian Virus 40 Large Tumor Antigen Fusion Gene.” Proc Natl Acad Sci USA 91: 11236—40.

Okazaki, R. , A. Sakai , A. Ootsuyama , T. Sakata , T. Nakamura , and T. Norimura (2003). “Apoptosis and p53 Expression in Chondrocytes Related to Degeneration in Articular Cartilage of Immobilized Knee Joints .” J Rheumatol 30: 559—66.

Qiao, J.-H. , R.B. Mertens , M.C. Fishbein , and S.A. Geller (2003). “Cartilagenous Metaplasia in Calcified Diabetic Peripheral Vascular Disease: Morphologic Evidence of Enchondral Ossification .” Hum Pathol 34: 402—7.

Qiao, J.-H. , M.C. Fishbein , L.L. Demer , and A.J. Lusis (1995). “Genetic Determination of Cartilaginous Metaplasia in Mouse Aorta.” Arterioscler Thromb Vasc Biol 15: 2265—72

Rossi, F. , H.E. MacLean , W. Yuan , R.O. Francis , E. Semenova , C.S. Lin , H.M. Kronenberg , and D. Cobrinik (2002). “p107 and p130 Coordinately Regulate Proliferation, Cbfa1 Expression, and Hypertrophic Differentiation During Endochondral Bone Development.” Dev Biol 247: 271—85.

Serra, R. , M. Johnson , E.H. Filvaroff , J. LaBorde , D.M. Sheehan , R. Derynck , and H.L. Moses (1997). “Expression of a Truncated, Kinase-Defective TGF-β Type II Receptor in Mouse Skeletal Tissue Promotes Terminal Chondrocyte Differentiation and Osteoarthritis.” J Cell Biol 139: 541—52.

Shibata, M.-A. , C.L. Jorcyk , M.-L. Liu , K. Yoshidome , L.G. Gold , and J.E. Green (1998). “The C3(1)/SV40 T Antigen Transgenic Mouse Model of Prostate and Mammary Cancer.” Toxicol Pathol 26: 177—82.

10.

Smith, R.K. , A. Coumbe , and M.C. Schramme (1995). “Bilateral Synovial Chondromatosis of the Metatarsophalangeal Joints in a Pony.” Equine Vet J 27: 234—8.

11.

Tse, J. , B. Martin-McNaulty , M. Halks-Miller , K. Kauser , V. DelVecchio , R. Vergona , M.E. Sullivan , and G.M. Rubanyi (1999). “Accelerated Atherosclerosis and Premature Calcified Cartilaginous Metaplasia in the Aorta of Diabetic Male Apo E Knockout Mice Can be Prevented by Chronic Treatment With 17 β -Estradiol.” Atherosclerosis 144: 303—13.

12.

Weaver, J.L. , J.F. Contrera , B.A. Rosenzweig , K.L. Thompson , P.J. Faustino , J.M. Strong , C.D. Ellison , L.W. Anderson , H.R. Prasanna , P.E. Long-Bradley , K.K. Lin , J. Zhang , and F.D. Sistare (1998). “An Evaluation of the Hemizygous Transgenic Tg.AC Mouse for Carcinogenicity Testing of Pharmaceuticals. I. Evidence for a Confounding Nonresponder Phenotype.” Toxicol Pathol 26: 532—40.

13.

Yang, Y.Z. , L. Topol , H. Lee , and J.L. Wu (2003). “Wnt5a and Wnt5b Exhibit Distinct Activities in Coordinating Chondrocyte Proliferation and Differentiation. ” Development 130: 1003—15.